Persistent serum protein signatures define an inflammatory subcategory of long COVID

Aarthi Talla, Suhas V. Vasaikar, Gregory Lee Szeto, Maria P. Lemos, Julie L. Czartoski, Hugh MacMillan, Zoe Moodie, Kristen W. Cohen, Lamar B. Fleming, Zachary Thomson, Lauren Okada, Lynne A. Becker, Ernest M. Coffey, Stephen C. Rosa, Evan W. Newell, Peter J. Skene, Xiaojun Li, Thomas F. Bumol (), M. Juliana McElrath () and Troy R. Torgerson ()
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Aarthi Talla: Allen Institute for Immunology
Suhas V. Vasaikar: Allen Institute for Immunology
Gregory Lee Szeto: Allen Institute for Immunology
Maria P. Lemos: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Julie L. Czartoski: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Hugh MacMillan: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Zoe Moodie: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Kristen W. Cohen: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Lamar B. Fleming: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Zachary Thomson: Allen Institute for Immunology
Lauren Okada: Allen Institute for Immunology
Lynne A. Becker: Allen Institute for Immunology
Ernest M. Coffey: Allen Institute for Immunology
Stephen C. Rosa: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Evan W. Newell: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Peter J. Skene: Allen Institute for Immunology
Xiaojun Li: Allen Institute for Immunology
Thomas F. Bumol: Allen Institute for Immunology
M. Juliana McElrath: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Troy R. Torgerson: Allen Institute for Immunology

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute SARS-CoV-2 infection. The aetiologies may include persistent inflammation, unresolved tissue damage or delayed clearance of viral protein or RNA, but the biological differences they represent are not fully understood. Here we evaluate the serum proteome in samples, longitudinally collected from 55 PASC individuals with symptoms lasting ≥60 days after onset of acute infection, in comparison to samples from symptomatically recovered SARS-CoV-2 infected and uninfected individuals. Our analysis indicates heterogeneity in PASC and identified subsets with distinct signatures of persistent inflammation. Type II interferon signaling and canonical NF-κB signaling (particularly associated with TNF), appear to be the most differentially enriched signaling pathways, distinguishing a group of patients characterized also by a persistent neutrophil activation signature. These findings help to clarify biological diversity within PASC, identify participants with molecular evidence of persistent inflammation, and highlight dominant pathways that may have diagnostic or therapeutic relevance, including a protein panel that we propose as having diagnostic utility for differentiating inflammatory and non-inflammatory PASC.

Date: 2023
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DOI: 10.1038/s41467-023-38682-4

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